Chronic periodontitis is a primary cause of tooth loss in adults. Periodontitis is normally caused by inflammation or infections of the gums (gingivitis), as well as the ligaments and bone that support the teeth. Loss of support causes the teeth to become loose and eventually fall out. The disease is also characterized by the presence of high levels of cytokines in the affected tissue of the gums.
Diabetes and hyperglycemia have been shown to have links to periodontal disease. For example, patients with type 2 diabetes have greater incidence and severity of periodontal disease than non-diabetics (Soskolne and Klinger, The relationship between periodontal diseases and diabetes: an overview. Ann. Periodontol., 6:91-98, 2001; Emrich et al., Periodontal disease in non-insulin-dependent diabetes mellitus. J. Periodontol., 62:123-31, 1991; Taylor et al., Impact of oral diseases on systemic health in the elderly: diabetes mellitus and aspiration pneumonia. J. Public Health Dent., 60:313-20, 2000; Oliver and Tervonen, Periodontitis and tooth loss: comparing diabetics with the general population. J. Am. Dent. Assoc., 124:71-76, 1993). A recent analysis of the National Health and Nutrition Examination Survey (NHANES) III data also showed that poor glycemic control in type 2 diabetes patients was associated with greater severity of periodontitis (Tsai et al., Glycemic control of type 2 diabetes and severe periodontal disease in the US adult population. Community Dent. Oral Epidemiol., 30:182-92, 2002). Furthermore, hyperglycemia has been thought to play a role in the incidence and prevalence of periodontal disease (Soskolne and Klinger, The relationship between periodontal diseases and diabetes: an overview. Ann. Periodontol., 6:91-98, 2001; Losche et al., Plasma lipid and blood glucose levels in patients with destructive periodontal disease. J. Clin. Periodontol., 27:537-41, 2000; Tervonen and Knuuttila, Relation of diabetes control to periodontal pocketing and alveolar bone level. Oral Surg. Oral Med. Oral Pathol., 61:346-49, 1986). Additionally, patients with relatively good glycemic control are less prone to periodontal destruction in longitudinal studies (Taylor et al., Severe periodontitis and risk for poor glycemic control in patients with non-insulin-dependent diabetes mellitus. J. Periodontol., 67:1085-93, 1996).
Early efforts to determine mechanisms that account for increased occurrence of periodontitis in diabetes mellitus focused on differences in the periodontal microflora. One report suggested that hyperglycemia was associated with an altered subgingival microbiota (Zambon et al., Microbiological and immunological studies of adult periodontitis in patients with noninsulin-dependent diabetes mellitus. J. Periodontol., 59:23-31, 1988). However, subsequent studies failed to identify differences in specific periodontal pathogens in diabetic versus non-diabetic subjects (Tervonen et al., Prevalence of periodontal pathogens with varying metabolic control of diabetes mellitus. J. Clin. Periodontol., 21:375-79, 1994; Yuan et al., Detection of putative periodontal pathogens in non-insulin-dependent diabetes mellitus and non-diabetes mellitus by polymerase chain reaction. J. Periodontal Res., 36:18-24, 2001).
Interleukin 1 (IL-1) is known to be a potent bone resorptive cytokine (Gowen and Mundy, Actions of recombinant interleukin 1, interleukin 2, and interferon-gamma on bone resorption in vitro. J. Immunol., 136:2478-82, 1986). Elevated levels of IL-1 in the gingival crevicular fluid (GCF) and gingival tissues have been associated with chronic periodontitis (Masada et al., Measurement of interleukin-1 alpha and -1 beta in gingival crevicular fluid: implications for the pathogenesis of periodontal disease. J. Periodontal Res., 25:156-63, 1990; Stashenko et al., Tissue levels of bone resorptive cytokines in periodontal disease. J. Periodontol., 62:504-09, 1991; Hou et al., Crevicular interleukin-1 beta in moderate and severe periodontitis patients and the effect of phase I periodontal treatment. J. Clin. Periodontol., 22:162-67, 1995; Mathur et al., Interleukin-1 alpha, interleukin-8 and interferon-alpha levels in gingival crevicular fluid. J. Periodontal Res., 31:489-95, 1996; Figueredo et al., Increased interleukin-1beta concentration in gingival crevicular fluid as a characteristic of periodontitis. J. Periodontol., 70:1457-63, 1999; Engebretson et al., The influence of interleukin gene polymorphism on expression of interleukin-1beta and tumor necrosis factor-alpha in periodontal tissue and gingival crevicular fluid. J. Periodontol., 70:567-73, 1999; Engebretson et al., GCF IL-1beta profiles in periodontal disease. J. Clin. Periodontol., 29:48-53, 2002). Several clinical studies have also demonstrated elevated inflammatory mediators, including IL-1, in the GCF of patients with type 1 diabetes, as compared with non-diabetic subjects (Kurtis et al., IL-6 levels in gingival crevicular fluid (GCF) from patients with non-insulin dependent diabetes mellitus (NIDDM), adult periodontitis and healthy subjects. J. Oral Sci., 41:163-67, 1999; Salvi et al., Inflammatory mediator response as a potential risk marker for periodontal diseases in insulin-dependent diabetes mellitus patients. J. Periodontol., 68:127-35, 1997; Salvi et al., PGE2, IL-1 beta, and TNF-alpha responses in diabetics as modifiers of periodontal disease expression. Ann. Periodontol., 3:40-50, 1998; Cutler et al., Heightened gingival inflammation and attachment loss in type 2 diabetics with hyperlipidemia. J. Periodontol., 70:1313-21, 1999).
Tumor necrosis factor (TNF) is a cytokine produced primarily by monocytes and macrophages. It, like other cytokines, is found in higher levels in people suffering from chronic periodontitis. TNF is also found in higher amounts within the plasma of patients with diabetes. Because TNF can adversely influence the insulin receptor and complicate glycemic control, it is desirable, from a diabetes-management perspective, to lower levels of TNF in a diabetes patient's circulation.